Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study

Le-Qing Cao; Wen-Xuan Huo; Er-Lie Jiang; Yue-Wen Fu; Xiao-Jun Xu; Ping-Chong Lei; Ming-Feng Zhao; Zhi Chen; Shu-Xia Guo; Xiao-Bing Huang; Yan-Ming Zhang; Xian-Jing Wang; Guan-Chen Bai; Feng-Bo Jin; Qing-Sheng Li; Ming-Yang Deng; Hao Zhang; Xin-Feng Wang; Xiao-Jun Huang; Xiao-Dong Mo

doi:10.1186/s40779-025-00640-0

Your Location：

Home >

Browse articles >

Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study

RESEARCH | Updated：2026-05-08

- Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study
- Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study
- Military Medical Research 2026年13卷第3期页码：400-412
- Affiliations：
  
  1.Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China
  2.State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China
  3.Department of Hematology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China
  4.Children’s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou 310052, China
  5.Department of Hematology, Henan Provincial People’s Hospital, Zhengzhou 450003, China
  6.Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China
  7.Department of Hematology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
  8.Department of Hematology, People’s Hospital of Zhengzhou, Zhengzhou 450003, China
  9.Department of Hematology, Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu 610072, China
  10.Department of Hematology, Huai’an Second People’s Hospital, Huai’an 223002, Jiangsu, China
  11.Department of Hematology, the Third People’s Hospital of Zhengzhou, Zhengzhou 450003, China
  12.Department of Hematology, the Affiliated Tai’an City Central Hospital of Qingdao University, Tai’an 271000, Shandong, China
  13.Anhui Public Health Clinical Center, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
  14.The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
  15.Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, China
  16.Department of Hematology, Affiliated Hospital of Jining Medical University, Jining 272067, Shandong, China
  17.Department of Hematology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
  18.Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
- Author bio：
  
  * Xiao-Dong Mo moxiaodong@pkuph.edu.cn
- Funds：
  
  the Beijing Natural Science Foundation(Z230016);the National Key Research and Development Program of China(2022YFA1103300;2022YFC2502606);the Major Program of the National Natural Science Foundation of China(82293630);the Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(71003Y3035);the Plan Project of Tongzhou Municipal Science and Technology(KJ2024CX045);the National Natural Science Foundation of China(82170208);the Talent Development Plan for the Future in Medical-Engineering Integration by the Beijing Research Association for Chronic Diseases Control and Health Education (BRA-CDCHE);the Fundamental Research Funds for the Central Universities
- DOI：10.1186/s40779-025-00640-0
  中图分类号：
- 收稿：2024-12-02，
  
  录用：2025-08-08，
  
  网络首发：2025-09-29，
  
  纸质出版：2026-03
- Accepted：
Scan QR Code
Le-Qing Cao, Wen-Xuan Huo, Er-Lie Jiang, 等. Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study[J]. Military Medical Research, 2026,13(3):400-412.

Le-Qing Cao, Wen-Xuan Huo, Er-Lie Jiang, et al. Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study[J]. Military Medical Research, 2026, 13(3): 400-412.
Le-Qing Cao, Wen-Xuan Huo, Er-Lie Jiang, 等. Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study[J]. Military Medical Research, 2026,13(3):400-412. DOI： 10.1186/s40779-025-00640-0.

Le-Qing Cao, Wen-Xuan Huo, Er-Lie Jiang, et al. Xenopax for the treatment of steroid-refractory acute graft-versus-host disease: the RELAX study[J]. Military Medical Research, 2026, 13(3): 400-412. DOI： 10.1186/s40779-025-00640-0.

摘要

Abstract

Background

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is the major cause of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Xenopax

a novel and the only available humanized interleukin-2 (IL-2) receptor antagonist

has been approved as a category 2 biological product by the National Medical Products Administration. This study aims to evaluate the efficacy

safety

and prognostic factors of xenopax treatment for SR-aGVHD in real-world settings.

Methods

This was a multicenter

retrospective analysis that included SR-aGVHD patients who received xenopax at 17 hospitals across China. The data were collected from the electronic medical records in transplant databases. The primary endpoint was the 28-day overall response rate (ORR)

encompassing both partial and complete responses. This study also included independent historical SR-aGVHD cohorts treated with best available treatments (BATs

= 1009) as controls.

Results

In total

172 SR-aGVHD patients were included in this study. Xenopax was administered either as monotherapy (

= 60) or in combination with other second-line treatments (

= 112). The ORR was 64.5% [95% confidence interval (CI) 57.3–71.7%

]

on day 28 and 82.6% (95% CI 76.9–88.3%) at any time after xenopax treatment. The 2-year probabilities of disease-free survival

overall survival

non-relapse mortality (NRM)

and relapse after xenopax treatment were 57.0% (95% CI 49.9–65.0%)

68.0% (95% CI 61.4–75.4%)

24.2% (95% CI 18.0–30.9%)

and 19.0% (95% CI 12.8–25.2%)

respectively. The ORR and survival were similar between patients with and without prior second-line treatments. The conditioning regimen and human leukocyte antigen disparity did not impact the efficacy of xenopax treatment. According to the multivariate analysis

the presence of grade III–IV aGVHD did not adversely affect the therapeutic response or survival. Xenopax also showed some superiority over BATs in historical cohorts.

Conclusions

Our real-world findings suggest that xenopax is an effective and safe treatment for SR-aGVHD.

关键词

Keywords

references

Wang Y , Gao X , Wang T , Zhang X , Xu L , Wang Y , et al . Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs. identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia . Chin J Cancer Res. 2024 ; 36 ( 5 ): 530 - 44 .

Xu ZL , Zhang YP , Ye BD , Zhao X , Zhou M , Lu PH , et al . Comparable survival outcomes in HLA-matched and haploidentical hematopoietic stem cell transplantation for severe aplastic anemia patients aged 40–50: a CBMTR registry-based propensity score matching analysis over the last decade . Cancer Lett. 2025 ; 621 : 217594 .

Wen Q , Jiang C , Liu X , Xia Y , Ma Y , Yang Y , et al . Venetoclax and azacitidine compared with intensive chemotherapy for adverse-risk acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation in first complete remission: a multicenter study of TROPHY group . Chin J Cancer Res. 2025 ; 37 ( 3 ): 417 - 31 .

Cao LQ , Huo WX , Zhang XH , Xu LP , Wang Y , Yan CH , et al . Peripheral blood stem cell transplantation from haploidentical related donor could achieve satisfactory clinical outcomes for intermediate- or highrisk adult acute myeloid leukemia patients . Bone Marrow Transplant. 2024 ; 59 ( 2 ): 203 - 10 .

Zeiser R , Blazar BR . Acute graft-versus-host disease - biologic process, prevention, and therapy . N Engl J Med. 2017 ; 377 ( 22 ): 2167 - 79 .

Gratwohl A , Brand R , Frassoni F , Rocha V , Niederwieser D , Reusser P , et al . Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time . Bone Marrow Transplant. 2005 ; 36 ( 9 ): 757 - 69 .

Garnett C , Apperley JF , Pavlu J . Treatment and management of graftversus-host disease: improving response and survival . Ther Adv Hematol. 2013 ; 4 ( 6 ): 366 - 78 .

Arai S , Margolis J , Zahurak M , Anders V , Vogelsang GB . Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment . Biol Blood Marrow Transplant. 2002 ; 8 ( 3 ): 155 - 60 .

Pidala J , Anasetti C . Glucocorticoid-refractory acute graft-versus-host disease . Biol Blood Marrow Transplant. 2010 ; 16 ( 11 ): 1504 - 18 .

Malard F , Huang XJ , Sim JPY . Treatment and unmet needs in steroidrefractory acute graft-versus-host disease . Leukemia. 2020 ; 34 ( 5 ): 1229 - 40 .

Deng D , Shen M , Zhang X , Xu L , Wang Y , Yan C , et al . Basiliximab is the potential solution for severe liver chronic GVHD: a prospective pilot study . The Innovation Medicine. 2023 ; 1 ( 1 ): 100009 .

Jiang XY , Zhang XH , Xu LP , Wang Y , Yan CH , Chen H , et al . Basiliximab treatment for patients with steroid-refractory acute graft-versus-host disease following matched sibling donor hematopoietic stem cell transplantation . Cell Transplant. 2024 ; 33 : 9636897241257568 .

Liu SN , Zhang XH , Xu LP , Wang Y , Yan CH , Chen H , et al . Prognostic factors and long-term follow-up of basiliximab for steroid-refractory acute graftversus-host disease: updated experience from a large-scale study . Am J Hematol. 2020 ; 95 ( 8 ): 927 - 36 .

Socie G , Vigouroux S , Yakoub-Agha I , Bay JO , Furst S , Bilger K , et al . A phase 3 randomized trial comparing inolimomab vs usual care in steroidresistant acute GVHD . Blood. 2017 ; 129 ( 5 ): 643 - 9 .

Ho VT , Zahrieh D , Hochberg E , Micale E , Levin J , Reynolds C , et al . Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation . Blood. 2004 ; 104 ( 4 ): 1224 - 6 .

Perales MA , Ishill N , Lomazow WA , Weinstock DM , Papadopoulos EB , Dastigir H , et al . Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease . Bone Marrow Transplant. 2007 ; 40 ( 5 ): 481 - 6 .

Mo XD , Hong SD , Zhao YL , Jiang EL , Chen J , Xu Y , et al . Basiliximab for steroid-refractory acute graft-versus-host disease: a real-world analysis . Am J Hematol. 2022 ; 97 ( 4 ): 458 - 69 .

Shen MZ , Li JX , Zhang XH , Xu LP , Wang Y , Liu KY , et al . Meta-analysis of interleukin-2 receptor antagonists as the treatment for steroid-refractory acute graft-versus-host disease . Front Immunol. 2021 ; 12 : 749266 .

Daclizumab withdrawn from the market worldwide . Drug Ther Bull. 2018 ; 56 ( 4 ): 38 .

Tao T , Ma X , Yang J , Zou JY , Ji SM , Tan YS , et al . Humanized anti-CD25 monoclonal antibody treatment of steroid-refractory acute graft-versus-host disease: a Chinese single-center experience in a group of 64 patients . Blood Cancer J. 2015 ; 5 ( 4 ): e308 .

Xu ZL , Han TT , Zhu XL , Liu J , Lv M , Sun YQ , et al . Randomized trial of antithymocyte globulin plus low-dose post-transplant cyclophosphamide to prevent graft-versus-host disease in haploidentical transplantation . Haematologica. 2020 . https://doi.org/10.3324/haematol.2025.287504 .

Booth CM , Karim S , Mackillop WJ . Real-world data: towards achieving the achievable in cancer care . Nat Rev Clin Oncol. 2019 ; 16 ( 5 ): 312 - 25 .

Zhang XH , Chen J , Han MZ , Huang H , Jiang EL , Jiang M , et al . The consensus from the Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update . J Hematol Oncol. 2021 ; 14 ( 1 ): 145 .

Hematopoietic Stem Cell Application Group . Chinese Society of Hematology, Chinese Medical Association. Chinese consensus of allogeneic hematopoietic stem cell transplantation for hematological disease(III)-acute graft-versus-host disease (2020) . Zhonghua Xue Ye Xue Za Zhi. 2020 ; 41 ( 7 ): 529 - 36 .

Schoemans HM , Lee SJ , Ferrara JL , Wolff D , Levine JE , Schultz KR , et al . EBMT-NIH-CIBMTR task force position statement on standardized terminology & guidance for graft-versus-host disease assessment . Bone Marrow Transplant. 2018 ; 53 ( 11 ): 1401 - 15 .

Dignan FL , Clark A , Amrolia P , Cornish J , Jackson G , Mahendra P , et al . Diagnosis and management of acute graft-versus-host disease . Br J Haematol. 2012 ; 158 ( 1 ): 30 - 45 .

Zeiser R , Von Bubnoff N , Butler J , Mohty M , Niederwieser D , Or R , et al . Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease . N Engl J Med. 2020 ; 382 ( 19 ): 1800 - 10 .

Shen MZ , Liu XX , Qiu ZY , Xu LP , Zhang XH , Wang Y , et al . Efficacy and safety of mesenchymal stem cells treatment for multidrug-resistant graftversus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation . Ther Adv Hematol. 2022 ; 13 : 20406207211072838 .

Zhao JY , Liu SN , Xu LP , Zhang XH , Wang Y , Chen YH , et al . Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide . Ann Hematol. 2021 ; 100 ( 1 ): 169 - 80 .

Jiang E , Qian K , Wang L , Yang D , Shao Y , Hu L , et al . Efficacy and safety of human umbilical cord-derived mesenchymal stem cells versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease: a multicentre, randomized, double-blind, phase 2 trial . BMC Med. 2024 ; 22 ( 1 ): 555 .

Jagasia M , Perales MA , Schroeder MA , Ali H , Shah NN , Chen YB , et al . Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial . Blood. 2020 ; 135 ( 20 ): 1739 - 49 .

Jagasia MH , Greinix HT , Arora M , Williams KM , Wolff D , Cowen EW , et al . National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The Diagnosis and Staging Working Group report . Biol Blood Marrow Transpl. 2015 ; 21 ( 3 ): 389 - 440 .

Gooley TA , Leisenring W , Crowley J , Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators . Stat Med. 1999 ; 18 ( 6 ): 695 - 706 .

Olyaei AJ , Thi K , Demattos AM , Bennett WM . Use of basiliximab and daclizumab in kidney transplantation . Prog Transpl. 2001 ; 11 ( 1 ): 33 - 7 .

Pascual J , Marcén R , Ortuño J . Anti-interleukin-2 receptor antibodies: basiliximab and daclizumab . Nephrol Dial Transplant. 2001 ; 16 ( 9 ): 1756 - 60 .

Fan S , Huo WX , Yang Y , Shen MZ , Mo XD . Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: a meta-analysis . Front Immunol. 2022 ; 13 : 954268 .

Zhang MY , Zhao P , Zhang Y , Wang JS . Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: systematic review and meta-analysis of randomised and non-randomised studies . PLoS ONE. 2022 ; 17 ( 7 ): e0271979 .

Baccelli F , Gottardi F , Muratore E , Leardini D , Grasso AG , Gori D , et al . Ruxolitinib for the treatment of acute and chronic graft-versus-host disease in children: a systematic review and individual patient data meta-analysis . Bone Marrow Transpl. 2024 ; 59 ( 6 ): 765 - 76 .

Penack O , Marchetti M , Aljurf M , Arat M , Bonifazi F , Duarte RF , et al . Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation . Lancet Haematol. 2024 ; 11 ( 2 ): e147 - 59 .

Hematopoietic Stem Cell Application Group , Chinese Society of Hematology , Chinese Medical Association . Chinese expert consensus on the diagnosis and treatment of acute graft-versus-host disease after hematopoietic stem cell transplantation (2024) . Zhonghua Xue Ye Xue Za Zhi. 2024 ; 45 ( 6 ): 525 - 33 .

Smallbone P , Mehta RS , Alousi A . Steroid refractory acute GVHD: the hope for a better tomorrow . Am J Hematol. 2025 ; 100 ( Suppl 3 ): 14 - 29 .

Inagaki J , Fukano R , Kodama Y , Nishimura M , Shimokawa M , Okamura J . Safety and efficacy of low-dose methotrexate for pediatric patients with steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation . Ann Hematol. 2014 ; 93 ( 4 ): 645 - 51 .

Zhang A , Huang Z , Zhang R , Wei R , Jiang S , Chen H , et al . Humanized anti-CD25 monoclonal antibody replaces methotrexate as acute graft-versushost disease prophylaxis in haploidentical allogeneic haematopoietic stem cell transplantation . Br J Haematol. 2025 ; 206 ( 2 ): 615 - 27 .

Lv M , Zhang X , Xu L , Wang Y , Yan C , Chen H , et al . Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia . Front Med. 2019 ; 13 ( 6 ): 667 - 79 .

Lastovytska I , Heidenreich S , Klyuchnikov E , Niederwieser C , Gagelmann N , Richter J , et al . Lower incidence of chronic graft-versus-host disease after ruxolitinib plus extracorporeal photopheresis versus ruxolitinib alone in steroid-refractory acute graft-versus-host disease following allogeneic stem cell transplantation . Haematologica. 2025 ; 110 ( 7 ): 1536 - 44 .

Zhao K , Lin R , Fan Z , Chen X , Wang Y , Huang F , et al . Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial . J Hematol Oncol. 2022 ; 15 ( 1 ): 22 .

Zhao Y , Wu H , Shi J , Luo Y , Li X , Lan J , et al . Ruxolitinib combined with etanercept induce a rapid response to corticosteroid-refractory severe acute graft vs host disease after allogeneic stem cell transplantation: results of a multi-center prospective study . Am J Hematol. 2020 ; 95 ( 9 ): 1075 - 84 .

Wu Y , Sun G , Tang B , Song K , Cheng Y , Tu M , et al . Ruxolitinib plus basiliximab therapy for steroid-refractory acute graft-versus-host disease in unrelated cord blood transplantation: a large-scale study . Transpl Cell Ther. 2024 ; 30 ( 9 ): 916.e1 - e12 .

Zhou F , Pan T , Li X , Du F , Ma X , Zhang Y , et al . Exploration of efficacy and safety of combined therapy of basiliximab with ruxolitinib for grade 3–4 steroid-refractory acute graft-versus-host disease: a registered clinical trial(NCT05021276) . Bone Marrow Transpl. 2023 ; 58 ( 8 ): 959 - 61 .

Zhang ZS , Liu YY , He SS , Bao DQ , Wang HC , Zhang J , et al . Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles . Mil Med Res. 2023 ; 10 ( 1 ): 13 .

Fu H , Sun X , Lin R , Wang Y , Xuan L , Yao H , et al . Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graftversus-host disease as a second-line therapy: a multicentre, randomized, controlled trial . BMC Med. 2024 ; 22 ( 1 ): 85 .

Liu X , Cao L , Wu X , Mo X . Vedolizumab provides a new hope of acute graft-versus-host disease prophylaxis through immune regulation . The Innov Med. 2024 ; 2 ( 3 ): 100083 .

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

暂无数据